VEGF/Ang2 inhibitor (BI 836880)

VEGF/Ang2 inhibitor (BI 836880)

BI 836880: a dual inhibitor of two key pathways mediating tumor angiogenesis

BI 836880* is a humanized bispecific nanobody® comprising blocking domains for vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang2).1 BI 836880 is a potent and selective inhibitor of VEGF and Ang2.1

Clinical trials (monotherapy and combination therapy): BI 836880 is currently being investigated as monotherapy in patients with solid tumors,2-4 and in combination with ezabenlimab (BI 754091)*, a programmed cell death protein-1 (PD-1) inhibitor, in patients with non-squamous non-small cell lung cancer (NSCLC) with programmed cell death ligand-1 (PD-L1) expression >1%, as well as in patients with other solid tumors.4,5

Role of VEGF/Ang2

VEGF and Ang2 signaling have different but complementary functions in tumor angiogenesis:6–8

  • Ang2 destabilizes established blood vessels through interruption of vascular tyrosine protein kinase receptor Tie2 signaling, which promotes vessel remodeling – a prerequisite for sprouting angiogenesis
  • Signaling via VEGF regulates endothelial cell proliferation and migration, and vessel sprouting

Preclinical studies in mouse models of various solid tumors have shown that combined VEGF/Ang2 blockade prolongs survival compared with blockade of either pathway alone.6

VEGF and Ang2 have complementary roles in tumor angiogenesis7,8

Role of Ang2 and VEGF in angiogenesis
Ang2, angiopoietin-2; VEGF, vascular endothelial growth factor; VEGFR, vascular endothelial growth factor receptor.

About BI 836880

Mechanism of action

BI 836880 is a humanized bispecific nanobody® (antibody fragments consisting of a single variable antibody domain) comprising blocking domains for VEGF and Ang2 and an additional portion for extending the half-life.1 By binding to VEGF and Ang2, BI 836880 inhibits tumor angiogenesis and vascularization, and enhances the tumor microenvironment to support T-cell trafficking and function in the tumor,1 making it a potential candidate for use in combination with PD-1 inhibitors (e.g. ezabenlimab).

Immunopermissive mechanism of action of dual VEGF/Ang2 inhibition1,6–8

VEGF/Ang2 mechanism of action
Ang2, angiopoietin-2; CD, cluster of differentiation; PD-1, programmed cell death protein-1; VEGF, vascular endothelial growth factor; VEGFR, vascular endothelial growth factor receptor.

Watch the VEGF/Ang2 inhibitor mechanism of action animation

Watch the VEGF/Ang2 inhibitor mechanism of action animation

Preclinical development

Preclinical data have shown that BI 836880 can potently and selectively neutralize VEGF and Ang2 in models of pancreatic, lung, renal, ovarian and colon cancer.1 Furthermore, BI 836880 showed superior inhibition of tumor growth and angiogenesis in vivo than either the VEGF inhibitor bevacizumab or the Ang1/2 inhibitor AMG 368 alone.1

Clinical development

BI 836880 is currently being investigated as a monotherapy in patients with solid tumors,2,3 and in combination with ezabenlimab in patients with advanced non-squamous NSCLC and PD-L1 expression >1%, in patients with advanced gastrointestinal tumors,9 and in patients with other solid tumors.4,5

More information about Boehringer Ingelheim oncology clinical trials can be found on the MyStudyWindow website. Relevant trials for our VEGF/Ang2 inhibitor include: BI 1336-0011.

VEGF/Ang2 inhibitor (BI 836880) clinical trials

CRC, colorectal cancer; GEC, gastro-esophageal adenocarcinoma; MSS, microsatellite stable; NSCLC, non-small cell lung cancer; PD-1, programmed cell death protein-1; PD-L1, programmed cell death ligand-1; MMRp, mismatch repair proficient.
Trial number Phase Treatment Patient population Status

NCT026741522

(1336.1)

I

BI 836880

Locally advanced or metastatic solid tumors

Completed

NCT026895053 (1336.6)

I

BI 836880

Locally advanced or metastatic solid tumors

Completed

NCT034684265 (1336.11)

I

BI 836880 + ezabenlimab (BI 754091)

Locally advanced or metastatic non-squamous NSCLC and other solid tumors

Recruiting

NCT03972150(1336.12)

I

BI 836880 + ezabenlimab (BI 754091)

Advanced, unresectable and/or metastatic solid tumors

Active, not recruiting

NCT036973049  (1381.9)

II

BI 836880 + ezabenlimab (BI 754091)

Advanced or metastatic solid tumors (i.e. gastric adenocarcinoma or GEC; primary/secondary PD-1-resistant tumors; MSS CRC; or MMRp/MSS endometrial tumors) with or without previous PD-(L)1 treatment

Recruiting

Explore our latest VEGF/Ang2 inhibitor data

Our latest data on the VEGF/Ang2 inhibitor (BI 836880) were presented at the European Society for Medical Oncology (ESMO) and American Society of Clinical Oncology (ASCO) congresses 2020, as well as the ASCO Gastrointestinal Cancers Symposium 2021.

 

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References

1

Hofmann I, et al. Poster presentation at the 8th Euro Global Summit on Cancer Therapy 2015.

2

ClinicalTrials.gov. NCT02674152. http://clinicaltrials.gov/ct2/show/NCT02674152 (Accessed: February 2021).

3

ClinicalTrials.gov. NCT02689505. http://clinicaltrials.gov/ct2/show/NCT02689505 (Accessed: February 2021).

4

ClinicalTrials.gov. NCT03972150. http://clinicaltrials.gov/ct2/show/NCT03972150 (Accessed: February 2021).

5

ClinicalTrials.gov. NCT03468426. https://clinicaltrials.gov/ct2/show/NCT03468426 (Accesssed: February 2021).

6

Fukumura D, et al. Nat Rev Clin Oncol 2018;15(5):325–40.

7

Gerald D, et al. Cancer Res 2013;73(6):1649–57.

8

Huang H, et al. Nat Rev Cancer 2010;10(8):575–85.

9

ClinicalTrials.gov. NCT03697304. https://clinicaltrials.gov/ct2/show/NCT03697304 (Accesssed: February 2021).

*This is an investigational compound and has not been approved. Its safety and efficacy have not been established.

 

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Page last updated: March 2021